Alvelestat for Bronchiolitis Obliterans Syndrome

Palo Alto (17 mi)

Overseen bySteven Z Pavletic, M.D.

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Trial Summary

What is the purpose of this trial?Background: Bronchiolitis obliterans syndrome (BOS) is a complication people can experience after hematopoietic stem cell transplant. It usually affects people with chronic graft versus host disease (cGVHD). This occurs when donor stem cells attack the cells of the person who received them. BOS reduces airflow and oxygen levels in the body. It may be caused by neutrophil elastase in the body. Researchers believe the new drug alvelestat (MPH966) may help. Objectives: To test the safety of alvelestat (MPH966) and see what dose best inhibits neutrophil elastase in people with BOS after a stem cell transplant. To study how well the best dose improves lung function in those people. Eligibility: Adults 18 and older who have had a hematopoietic stem cell transplant and have cGVHD and BOS. Design: Participants will be screened with a medical history, physical exam, and blood and urine tests. They will have lung function and heart function tests. They will have computed tomography scans of the chest. Study part 1: Participants will take the starting dose of the study drug by mouth twice a day for 14 days. This is 1 cycle. They will get different doses, for up to 4 cycles. Study part 2: Participants will take the study drug twice a day by mouth at the dose set in part 1, for up to 12 months. Participants will keep medicine diaries. Participants will have several study visits. These may include: Repeats of the screening tests. Bronchoscopy with bronchoalveolar lavage. Sputum samples taken. 6-minute walking test. cGVHD assessment and answer questions. Participants will be contacted after the study for up to 24 months.

Eligibility Criteria

Adults over 18 who've had a stem cell transplant and suffer from chronic graft versus host disease (cGVHD) with Bronchiolitis Obliterans Syndrome (BOS). They must have been treated for cGVHD, have certain lung function test results, stable organ/marrow function, and agree to contraception. Excluded are those with recent malignancy treatments, uncontrolled illnesses, pregnancy/breastfeeding, prior neutrophil elastase inhibitors use or significant alcohol consumption.

Inclusion Criteria

I have been on a specific treatment for at least 3 months before joining.

I am 18 years old or older.

I have been diagnosed with BOS based on specific criteria.

I can care for myself but may need occasional help.

I have had a stem cell transplant and suffer from moderate to severe chronic GVHD.

Exclusion Criteria

I have non-alcoholic fatty liver disease or have been on related medication for over 2 weeks in the last year.

I have used neutrophil elastase inhibitors before.

My cancer has come back or gotten worse and needs treatment.

I have a history of liver problems, including cirrhosis or swelling in my abdomen.

Treatment Details

The trial is testing alvelestat (MPH966), which may inhibit neutrophil elastase that's thought to contribute to BOS after stem cell transplants. It involves two parts: varying doses over cycles up to 4 months followed by the best dose for up to a year. Participants will undergo extensive monitoring including lung/heart tests and bronchoscopy.

2Treatment groups

Experimental Treatment

Group I: Phase 2Experimental Treatment1 Intervention

MTD po bid on days 1-28

Group II: Phase 1bExperimental Treatment1 Intervention

Phase Ib dose escalation